The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. Source: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010 Converted to human by GenMAPP.org This pathway was inferred from Homo sapiens pathway [http://www.wikipathways.org/index.php?title=Pathway:WP382&oldid=28779 WP382(r28779)] with a 91% conversion rate. a74 f20 b95 d24 d71 ecb a36 c2b b12 a3c b3c ea5 mitogen activated protein kinase signaling pathway PW:0000007 Pathway Ontology 11749383 PubMed MAP kinases. Chem Rev 2001 Chen Z Gibson TB Robinson F Silvestro L Pearson G Xu B Wright A Vanderbilt C Cobb MH 12191611 PubMed Docking interactions in the mitogen-activated protein kinase cascades. Pharmacol Ther 2002 Tanoue T Nishida E 12947395 PubMed MAPK pathways in radiation responses. Oncogene 2003 Dent P Yacoub A Fisher PB Hagan MP Grant S 12676795 PubMed Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 2003 Huang EJ Reichardt LF 11369511 PubMed Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38. Cell Signal 2001 Harper SJ LoGrasso P 12390245 PubMed Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system. Genes Cells 2002 Takeda K Ichijo H 14597384 PubMed Transcriptional regulation by the MAP kinase signaling cascades. Gene 2003 Yang SH Sharrocks AD Whitmarsh AJ 12566928 PubMed The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals 2002 Zhu X Lee HG Raina AK Perry G Smith MA 12849693 PubMed Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line. Toxicol Lett 2003 Cho H Lee J Kwak NJ Lee KH Rha S Kim YH Cho YY Yang KH Kim K Lim Y 10618718 PubMed Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 - Crk signaling complex formation. Oncogene 1999 Garcia-Guzman M Dolfi F Zeh K Vuori K 21384452 PubMed GST pi modulates JNK activity through a direct interaction with JNK substrate, ATF2. Protein Sci 2011 Thévenin AF Zony CL Bahnson BJ Colman RF 17726008 PubMed MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta. J Biol Chem 2007 Abell AN Granger DA Johnson GL